Expert opinion on the use of transvaginal sonography for presurgical staging and classification of endometriosis.

Gynecological ultrasonography plays a central role in the management of endometriosis. The rapid technical development as well as the currently increasing evidence for non-invasive diagnostic methods require an updated compilation of recommendations for the use of ultrasound in the management of endometriosis. The present work aims to highlight the accuracy of sonography for diagnosing and classifying endometriosis and will formulate the present list of key messages and recommendations. This paper aims to demonstrate the accuracy of TVS in the diagnosis and classification of endometriosis and to discuss the clinical applications and consequences of TVS findings for indication, surgical planning and assessment of associated risk factors. (1) Sophisticated ultrasound is the primary imaging modality recommended for suspected endometriosis. The examination procedure should be performed according to the IDEA Consensus. (2) Surgical intervention to confirm the diagnosis alone is not recommended. A preoperative imaging procedure with TVS and/or MRI is strongly recommended. (3) Ultrasound examination does not allow the definitive exclusion of endometriosis. (4) The examination is primarily transvaginal and should always be combined with a speculum and a bimanual examination. (5) Additional transabdominal ultrasonography may enhance the accuracy of the examination in case of extra pelvic disease, extensive findings or limited transvaginal access. (6) Sonographic assessment of both kidneys is mandatory when deep endometriosis (DE) and endometrioma are suspected. (7) Endometriomas are well defined by sonographic criteria. When evaluating the ovaries, the use of IOTA criteria is recommended. (8) The description of sonographic findings of deep endometriosis should be systematically recorded and performed using IDEA terminology. (9) Adenomyosis uteri has sonographically well-defined criteria (MUSA) that allow for detection with high sensitivity and specificity. MRI is not superior to differentiated skilled ultrasonography. (10) Classification of the extent of findings should be done according to the #Enzian classification. The current data situation proves the best possible prediction of the intraoperative situs of endometriosis (exclusive peritoneum) for the non-invasive application of the #Enzian classification. (11) Transvaginal sonographic examination by an experienced examiner is not inferior to MRI diagnostics regarding sensitivity and specificity in the prediction of the extent of deep endometriosis. (12) The major advantage of non-invasive imaging and classification of endometriosis is the differentiated planning or possible avoidance of surgical interventions. The recommendations represent the opinion of experts in the field of non-invasive and invasive diagnostics as well as therapy of endometriosis. They were developed with the participation of the following national and international societies: DEGUM, ÖGUM, SGUM, SEF, AGEM/DGGG, and EEL.

Using trends in electronic recordings of vital signs to identify patients stable for transfer from acute hospitals.

Patients who are stable might not be required to remain in hospital. We aimed to create objective criteria to indicate stability based on vital signs. An index based on NEWS (NBI) was compared to a Patient Stability Index (PSI) algorithm created by random forest analysis. Data from the VITAL II study was used to train the algorithm and data from the VITAL III study to validate it. Failure rate of the algorithms was set close to the rate of readmission to UK hospitals at 15%. After a training period of two days the NBI identified stability with acceptable failure rates only after a further 96 hours with a subsequent release of 2143 bed days compared to the PSI which identified stability after only 12 hours leading to potential earlier release of 2652 bed days. Vital sign-based algorithms might be able to predict safe transfer from hospital and inform management of flow.

Assessment of Midfacial Hypoplasia in Down Syndrome Fetuses - Validity of a Two-Line Approach and Introduction of a Novel Angle (Maxilla-Mandible-Nasion Angle).

PURPOSE: To scrutinize the validity of a novel angle (maxilla-mandible-nasion angle, MMN) as objective proof of midfacial hypoplasia in trisomy 21 fetuses. MATERIALS AND METHODS: Volume data sets of 2(nd) trimester fetuses were reviewed in this retrospective study. After achievement of the correct midsagittal position, the fetal profile line (FP line) and the mandibulo-maxillary line (MML) were applied and the resulting angle was calculated. Additionally, the prefrontal space ratio (PFSR) was assessed. Both measurements were obtained from 401 euploid fetuses and 42 fetuses with trisomy 21. Values for MMN and PFSR<5(th) percentile were considered abnormal. RESULTS: The study included 443 fetuses with a mean gestational age of 21.3 weeks (range: 14.0-26.3). The MMN angle sufficiently identified hypoplasia of the midface in trisomy 21 fetuses (mean: 14.6°; range: 10.1°- 22.0°) compared to controls (mean: 20.5°; range: 17.3°-23.7°; p<0.0001). Concomitantly, the PFSR of Down syndrome fetuses was significantly lower (mean: 0.53; range: 0.21-1.22) than in euploid individuals (1.38; range: 0.54-2.23; p<0.0001). CONCLUSION: Calculation of the novel MMN angle in 2(nd) trimester fetuses reliably allows rapid assessment of craniofacial anatomy in order to rule out the midfacial hypoplasia frequently found in trisomy 21.

Treatment-Associated Anxiety among Pregnant Women and their Partners: What is the Influence of Sex, Parity, Age and Education?

BACKGROUND: Anxiety during pregnancy can influence outcomes negatively. The aim of this study was to assess the fears of expectant parents in the setting of antenatal and obstetric care according to their sex, age, parity and education. METHODS: 259 pregnant women and 183 partners, who had presented for antenatal investigation, routine antenatal care or for delivery in the UKSH women's hospital, Lübeck campus, completed a self-assessment questionnaire of fears and the German version of the STAI (Laux et al.). ANOVA and t-tests were used for significance testing. RESULTS: Pregnant women had higher levels of trait anxiety and state anxiety than their partners. Level of education had a significant, inverse effect on trait anxiety. Age had no influence. Fears for the child's health ranked highest among pregnancy-specific fears. Expectant fathers had the same level of anxiety for the birth irrespective of parity; for women fear of the birth decreased with increasing parity. Anxiety only increased significantly for expectant fathers from the 20th week of gestation onwards. CONCLUSIONS: Pregnant women and their partners have different levels of anxiety dependant on their age, education, parity and the stage of pregnancy. These findings could contribute towards improving support of couples during pregnancy. The fears of expectant fathers require particular attention.

Therapeutic management of evans syndrome in a pregnancy with maternal systemic lupus erythematosus.

A 31-year-old 2 G 1 P was referred to our unit of prenatal medicine at 35+3 weeks of gestation with a spontaneously conceived singleton pregnancy of a female fetus without detectable anomalies. Maternal hematological evaluation revealed an Evans-syndrome-related thrombocytopenia based on a lupus erythematosus. The former delivery was aggravated by a severe hemorrhage several years before. Anti-autoimmunologic therapy was started and maternal platelets count increased to physiological values. Uneventful ceasarean section was performed at 37 weeks of gestation with favourable outcome for mother and child. This case is the first report of a successful therapy in maternal Evans syndrome in pregnancy combined with a lupus erythematosus.

Novel insights into early embryonic demise via 3D surface rendered imaging in 107 cases.

PURPOSE: Sonographic imaging techniques including 3 D volumetry were evaluated in women with missed abortion. Special emphasis was put on the impact of additional information regarding the etiology of the demise and improved visualization of embryonic and fetal anomalies due to the application of the latest imaging tools, e. g. HD live™. Parental acceptance of a more realistic display of the embryo/fetus in missed abortion was analyzed. MATERIALS AND METHODS: Between 09/2009 and 09/2012, 107 pregnancies with a missed abortion in the first trimester were included in this prospective survey. Using a transvaginal approach, all 2 D and 3 D studies were carried out with high-resolution 5 - 9 and 6 - 12 MHz probes. RESULTS: The mean gestational age was 70.3 days (49 - 110 days). The difference between estimated gestational age and sonographic age at evaluation for missed abortion was 13.5 days (-13 - 40 days). Additional information via three-dimensional volume acquisition, like craniofacial deformities, clefts, neural tube defects, abdominal wall defects and caudal regression syndrome, could be documented in 23/107 cases (21.5 %). In 2/107 cases the parents disapproved of the 3 D visualization due to the more realistic presentation. CONCLUSION: 3 D ultrasound in cases of missed abortion can provide additional information regarding the presence of structural anomalies. It may give further details regarding the timing of embryonic/fetal demise in early pregnancy. Sufficient informational value is regularly obtained in cases having a CRL > 8 mm. In counseling parents, 3 D ultrasound is a useful tool and is generally well accepted.

Outcome after second-trimester amniocentesis and first-trimester chorionic villus sampling for prenatal diagnosis in multiple gestations.

PURPOSE: The purpose of this study was to classify pregnancy loss and fetal loss as well as the influence of maternal risk factors in multiple pregnancies. METHODS AND MATERIALS: Details of the procedure and pregnancy outcome of all patients were extracted from the clinical audit database of two tertiary centers. The files were collected in the time from January 1993 to May 2011.  The procedure-related pregnancy and fetal loss rate was classified as all unplanned abortions without important fetal abnormalities or obstetric complications within 14 days after AC and CVS. RESULTS: We had a total number of 288 multiple pregnancies with a total of 637 fetuses. After the exclusion of 112 pregnancies with abnormal karyotype or fetal abnormalities detected by ultrasound as well as cases of selective feticide, repeated invasive procedures and monochorionic-monoamniotic pregnancies, 176 pregnancies and 380 fetuses were left for final analysis. Overall 132 amniocenteses and 44 chorionic villous sampling procedures were performed. The total pregnancy loss rate was 8.0 % (14/176), 6.1 % (n = 8) for amniocentesis and 13.6 % (n = 6) for CVS.  The procedure-related pregnancy loss rate was 3.4 %, 2.3 % after amniocentesis (3 cases) and 6.8 % after CVS (3 cases). There was no statistical significance between the two procedures (p = 0.15). CONCLUSION: The procedure-related loss rate of 3.4 % can be compared to the rates in the literature. The higher loss rates in multiple pregnancies than in singleton pregnancies have to be discussed when counseling parents.

PIK3CA and APC mutations are synergistic in the development of intestinal cancers.

Human colorectal cancers are known to possess multiple mutations, though how these mutations interact in tumor development and progression has not been fully investigated. We have previously described the FCPIK3ca* murine colon cancer model, which expresses a constitutively activated phosphoinositide-3 kinase (PI3K) in the intestinal epithelium. The expression of this dominantly active form of PI3K results in hyperplasia and invasive mucinous adenocarcinomas. These cancers form via a non-canonical mechanism of tumor initiation that is mediated through activation of PI3K and not through aberrations in WNT signaling. Since the Adenomatous Polyposis Coli (APC) gene is mutated in the majority of human colon cancers and often occurs simultaneously with PIK3CA mutations, we sought to better understand the interaction between APC and PIK3CA mutations in the mammalian intestine. In this study, we have generated mice in which the expression of a constitutively active PI3K and the loss of APC occur simultaneously in the distal small intestine and colon. Here, we demonstrate that expression of a dominant active PI3K synergizes with loss of APC activity resulting in a dramatic change in tumor multiplicity, size, morphology and invasiveness. Activation of the PI3K pathway is not able to directly activate WNT signaling through the nuclear localization of CTNNB1 (ß-catenin) in the absence of aberrant WNT signaling. Alterations at the transcriptional level, including increased CCND1, may be the etiology of synergy between these activated pathways.

Pregnancy risk factors for very premature delivery: what role do hypertension, obesity and diabetes play?

PURPOSE: Very premature delivery is a major cause of infant morbidity and mortality. Obesity, diabetes and pregnancy hypertension are known risk factors for pregnancy complications. The study aimed to scrutinize differences of pregnancy complications in a cohort of very premature deliveries compared to a national group. METHODS: In a multicenter study performed between January 2009 and December 2010 including 1,577 very low birth weight (VLBW) infants, we compared parental reported pregnancy problems of VLBW infants with a national cohort (KIGGS). We compared reported pregnancy complications to reasons for premature delivery and neonatal outcome within the group of VLBW infants. RESULTS: While parents of the national cohort reported pregnancy-induced hypertension in 8 %, parents of VLBW infants reported this complication more frequently (27 %). Mothers of the national cohort were significantly younger (1 year), suffered less from obesity, anaemia, diabetes. Regression analysis showed that hypertension (OR = 5.11) and advanced maternal age (OR = 1.03) increased the risk for premature birth. Women with hypertension were likely to experience a clinically indicated premature delivery, had more VLBW infants with a moderate growth restriction, but less multiples and their infants had less intraventricular haemorrhages grade 3 or 4. Otherwise, neonatal outcome was correlated with gestational age but not with the pregnancy complications diabetes, hypertension or obesity. CONCLUSION: Premature birth seems to be correlated to gestational hypertension and associated problems in about » of VLBW infants. Further studies should focus on preventing and treating gestational hypertension to avoid premature delivery and associated neonatal morbidity.

Fetal diagnosis of hypoplastic left heart, associations and outcomes in the current era.

PURPOSE: Hypoplastic left heart (HLH) is one of the most common forms of cardiac abnormality detectable during gestation by fetal echocardiography. Antenatal diagnosis allows for appropriate counseling and time to consider treatment options. We report the actual outcome data after fetal diagnosis of HLH. MATERIALS AND METHODS: Retrospective analysis of the outcome in all cases with HLH from 1994 - 2011 presenting in fetal life at two tertiary referral centers for prenatal diagnosis and pediatric cardiology. RESULTS: 105 cases were included and the overall survival is 40.9 % (43/105) after prenatal diagnosis. There was an 81.1 % survival rate in infants undergoing surgery and a 64.1 % survival rate from an intention-to-treat position. Two neonates died due to tamponade and cardiac arrest following balloon septostomy and one neonate from sepsis before surgery. Extracardiac anomalies occurred in three fetuses, and karyotype anomalies in seven fetuses (18.9 %). In 4 of 5 babies born with additional extracradiac or karyotype anomalies, parents opted for compassionate care. The first had trisomy 13, the second had trisomy 18, the third neonate presented with spina bifida, and the fourth presented with hydronephrosis and pulmonary atresia. Termination of pregnancy took place in 17 cases (16.1 %). CONCLUSION: Thorough antenatal evaluation should include karyotyping, detailed extracardiac and intracardiac assessment to accurately predict the risks of surgery. Prenatal counseling might be modified after the exclusion of additional anomalies. These data provide up-to-date information for parental counseling.

[Atypical myometric fluid accumulation in graviditate--intramural pregnancy or degenerated fibroid?]. / Atypischer myometraner Flüssigkeitsverhalt in graviditate--intramurale Schwangerschaft oder degeneriertes Myom?

We wish to discuss a case of suspected fluid accumulation within the anterior uterine wall in graviditate. The initial diagnosis of a rare intramural pregnancy could not be confirmed by 4+5 gestational weeks. Following removal of the fluid and establishing the diagnosis of degenerated fibroid(s), the advancing pregnancy was somewhat uneventful, whereas the uterine wall lesion showed continuing growth. Both during delivery (via Caesarean section) and on repeated sonographic scans post partum the clinical diagnosis of uterine wall fibroids could be confirmed. The present case illustrates the feasibility of expectant monitoring of atypical fybroids in pregnancy. Nevertheless, a thorough sonographic monitoring as well as comprehensive counselling of the gravida is mandatory. Potentially more serious differential diagnoses (intramural pregnancy, uterine sarcoma) should be born in mind.

Fetal loss rate and associated risk factors after amniocentesis, chorionic villus sampling and fetal blood sampling.

PURPOSE: To assess the total and procedure-related fetal loss rate and associated risk factors following amniocentesis (AC), chorionic villus sampling (CVS) and fetal blood sampling (FBS). MATERIALS AND METHODS: We performed a retrospective analysis of patients with invasive diagnostics from 1993 to 2011 in two tertiary referral centers. We aimed to classify pregnancy loss after an invasive procedure and included the time after the invasive procedure and the result of targeted ultrasound/karyotype analysis in the analysis. Fetal losses occurring within two weeks after an invasive procedure were classified as procedure-related. RESULTS: After excluding 1553 pregnancies with abnormal karyotype, fetal malformations and multiple insertions, 6256 cases were retrieved for final analysis. The total fetal loss rate was 1.5 %. The procedure-related fetal loss rate was 0.4 % for AC, 1.1 % for CVS and 0.4 % for FBS. Maternal vaginal bleeding in the first trimester was significantly associated with an increased procedure-related fetal loss rate (p= 0.008). The number of invasive procedures declined during the study period with increasing numbers of CVS in the first trimester. CONCLUSION: In our population the procedure-related fetal loss rate was 0.4 % after AC and 1.1 % and 0.4 % after CVS and FBS, respectively. Different gestational ages at the time of invasive procedures might account in part for those differences. Vaginal bleeding during the first trimester is associated with increased procedure-related fetal loss. Overall, declining numbers of invasive procedures are the result of changing attitudes toward invasive procedures and more sophisticated noninvasive prenatal screening programs over the last 20 years.

[Long-term outcome of children with prenatal diagnosed tachyarrhythmia]. / Langzeit-Outcome von Kindern mit pränatal diagnostizierter Tachyarrhythmie.

PURPOSE: The aim of this study was the follow-up of children with a prenatal diagnosis of tachyarrhythmia up to an age of 5 years in order to assess the long-term outcome of these children. MATERIALS AND METHODS: All fetuses diagnosed with prenatal tachyarrhythmia between April 1993 and June 2004 in the Division of Prenatal Medicine, Department of Obstetrics and Gynecology, University Hospital of Schleswig-Holstein, Campus Lübeck were identified and the children's parents and pediatricians were contacted for retrospective data on the children's health. The data from the compulsory examinations (U1-U9) were used for analysis. RESULTS: 49 cases (93%) were enrolled in this study. 23 fetuses had supraventricular tachycardia (SVT), 10 had an atrial flutter (AF) and 16 had paroxysmal supraventricular tachycardia (pSVT). Intrauterine conversion into sinus rhythm was achieved in 41 of 44 treated fetuses (93%). 17 of 48 cases showed tachyarrhythmia postnatally (35%). 15 of these newborns were treated with antiarrhythmic medication between 4 days and 46 months. The follow-up rate in the 3 subgroups ranged from 78-100%. At the time of the U9 examination, 69-100% of the children were healthy. During the examinations there was an increase in motor activity delay and language development delay with a maximum at U5 and U9, respectively. CONCLUSION: Overall, on the basis of the long-term follow-up of 49 children, we could show that prenatal tachyarrhythmia has a good prognosis. Increased motor activity and language development delay are important for patient counseling. Substantial cardiac and extracardiac anomalies are associated with an unfavorable outcome.

Teenage deliveries in Northern Germany: always a risk factor for higher surgical delivery rates?

PURPOSE: To evaluate the impact of young maternal age on labour, intrapartum assessment and delivery mode. METHODS: A retrospective cohort analysis was conducted of 13,941 deliveries at a tertiary delivery unit between 2000 and 2009. Patients aged less than 18 years were compared with patients aged 18 years or older. The main outcome was defined as mode of delivery. Frequencies and odds ratios for adverse maternal-foetal outcomes were calculated for primiparous women. RESULTS: Of the deliveries occurring during the study period, 6,863 (49.2%) met the inclusion criteria. A total of 156 deliveries (2.3%) occurred among teenagers less than 18 years and 6,707 among patients 18 years and older. Compared with patients 18 years of age and older, younger maternal age was associated with a higher chance of spontaneous delivery [adjusted odds ratio (OR) 2.07, 95% confidence interval (CI) 1.45-2.93] than via operation (vaginal operative delivery: OR 0.98, 95% CI 0.48-2.03; secondary caesarean delivery: adjusted OR 0.51, 95% CI 0.32-0.82). CONCLUSION: Young maternal age at delivery does not represent a risk factor for high surgical delivery rates.

Persistent right umbilical vein: a prenatal condition worth mentioning?

OBJECTIVES: To investigate the incidence and clinical impact of prenatally diagnosed persistent right umbilical vein (PRUV) in a referral population and to evaluate the findings together with those from previous publications. METHODS: This was a retrospective analysis of 39 cases with PRUV diagnosed in three tertiary referral centers for prenatal medicine between 1996 and 2009. Fetuses with situs inversus, situs ambiguous and heterotaxy (left and right isomerism) were excluded. During the study period 46 653 consecutive high- and low-risk pregnancies were examined. The prenatal sonograms and neonatal outcome data of affected individuals were reviewed. Our findings were analyzed together with findings retrieved from the scientific literature. RESULTS: Twenty-nine fetuses had an isolated PRUV as a single anomaly, whereas 10/39 (25.6%) were found to have PRUV accompanied by additional minor and major abnormalities. These anomalies comprised mainly cardiovascular, genitourinary and gastrointestinal malformations. In common with our series, previously published cases of isolated PRUV (n = 197) displayed an uneventful course of pregnancy and a favorable postnatal outcome. Sixty-six previously reported cases of PRUV with additional anomalies were identified in the literature. Intrahepatic umbilical drainage is the most frequent type of PRUV. Including our cases, there were 16 cases (5.3%) with extrahepatic drainage of PRUV, all of which had additional anomalies. CONCLUSIONS: Consistent with previous reports, in the majority of cases (74.8%) PRUV is an isolated finding. While these cases carry an excellent prognosis, PRUV can be associated with severe congenital anomalies, so this finding should prompt detailed prenatal assessment of the fetus.

Aneurysms of the fetal heart.

Aneurysmatic bulgings of either ventricular/atrial structures or outflow tract vessels such as the ductus arteriosus are rare prenatal conditions. Prenatal diagnosis is confirmed by detailed echocardiographic examination of the fetal heart. The majority of these congenital abnormalities are probably related to developmental disorders. Most of the affected fetuses display an asymptomatic course antenatally and postnatally. Associated anomalies include additional cardiac and extracardiac malformations with potential impact on normal development in fetal and neonatal life as well as early childhood. Treatment considerations have to be individually specified and depend on the presence and severity of clinical issues.

Seasonality of spina bifida in Northern Germany.

PURPOSE: To verify a seasonal variation in the incidence of spina bifida and thus to identify possible environmental triggers leading to its developement. METHODS: An interdisciplinary approach has been taken to develop a better understanding of spina bifida through collaborative efforts from investigators specializing in genetics, fetal pathology, paediatrics, neuro-surgery and prenatal ultrasonographic diagnosis. All pregnancies with fetal spina bifida were retrospectively analyzed from May 1 1993 through May 1 2010 at Luebeck University Fetal Health Center. Results were used to construct a model to predict the occurrence of fetal spina bifida based on seasonal variation and environmental influence reflected by climatic changes and environmental pollution. Furthermore, data were categorized in respect to the date of conception and subdivided into date of conception during summer (April-September) and winter months (October-March). RESULTS: Neither a seasonal distribution of conception for fetuses with spina bifida in the defined time frame could be verified nor a relevant influence of the analyzed environmental factors on the prevalence of spina bifida could be proved. The incidence of spina bifida has remained relatively stable within the last 17 years at 2.5 per 1,000 screened pregnancies. CONCLUSION: Since we were unable to demonstrate a relationship between seasonal variation and certain environmental factors on the incidence of fetal spina bifida, other factors should be investigated for a possible association with the onset of fetal spina bifida.

[Congenital gastroschisis--prenatal diagnosis and perinatal management]. / Kongenitale Gastroschisis--pränatale Diagnose und perinatales Management.

The birth prevalence of gastroschisis is increasing world-wide. This situation applies particularly to young, slim women who smoke. At a first glance this is a paradox in light of the ever-increasing age of pregnant women among whom there are fewer and fewer smokers. In numerous studies it has been clearly demonstrated that not only (nutritional) teratogenic substances and environmental factors but also epidemiological causes can be held responsible for this phenomenon. Nowadays gastroschisis is detected prenatally in up to 90% of all foetuses. Advantages of a prenatal diagnosis include the identification of associated disorders and the determination of a high-risk constellation (IUGR, intraabdominal bowel dilatation or vanishing gut). This is essential for an adequate interdisciplinary counseling for the afflicted parents together with obstetricians, paediatric surgeons and neonatalogists. The efficacy of serial amnioexchanges with regard to a better neonatal outcome has as yet not been unambiguously clarified. The possibilities for surgical procedures on the foetus are limited and can at present only be considered as experimental attempts in animal models. From an obstetrical perspective the in utero transport and elective Caesarean section before completion of the 36 (th) week of gestation in a tertiary centre with appropriate facilities (paediatric surgery, neonatalogy) seem to be the course recommended by most authors in spite of inconclusive data. The survival rates for babies with gastroschisis after operative treatment (primary defect closure, silotechnique) are considerably high (>90%).